Definition

KRAS encodes a GTPase protein downstream of the EGFR signaling pathway; activating mutations in regions such as exon 1 (codon 12/13) keep the protein continuously active, generating cell proliferation signals independent of EGFR. Approximately 35-45% of patients with metastatic colorectal cancer carry a KRAS mutation, and these patients do not benefit from anti-EGFR therapy such as cetuximab.

Gene/region examined

KRAS Exon 1, KRAS Exon 2, KRAS Exon 3, KRAS Exon 4, KRAS Exon 5, KRAS Exon 6

Method

DNA analysis

Accepted sample types

Fresh tumor tissue, Paraffin block

Description

Colorectal Cancers, Non-Small Cell Lung Cancer (NSCLC), Gastric Cancer, Familial Breast Cancer, Acute Myeloid Leukemia (AML), Pancreatic Carcinoma, Transitional Cell Bladder Cancer. Response to drug therapy: Erbitux (Cetuximab), Vectibix (Panitumumab), Tarceva (Erlotinib), Iressa (Gefitinib), Avastin (Bevacizumab).

Inheritance

KRAS mutations in colorectal cancer are somatic; they are acquired in tumor tissue, and new (secondary) mutations may also emerge during treatment, leading to acquired resistance.

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Inheritance Patterns

Describes how a genetic condition is passed on within a family. There are five main patterns

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Carrier (Heterozygous / Homozygous)

Why it matters: In autosomal recessive inheritance, when each parent is a carrier (while both appear healthy), the chance of their child being born with the disease is 25% in each

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VUS (Variant of Uncertain Significance)

This is the situation where the test has detected a change in the DNA, but the role of this change in the development of disease is unconfirmed.

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How to Read a Genetic Test Result (Positive / Negative / VUS)

A genetic test result falls into three main categories

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Types of Genetic Tests

A genetic test is a type of medical test that detects changes in genes, chromosomes or proteins. Today there are more than 77,000 genetic tests available.

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